The long-term objective of the proposed research is to evaluate hypoalgesia as a biobehavioral marker of risk for hypertension. The research will test the hypothesis that hypoalgesia and hypertension share a common pathophysiology (i.e., central opioid hyposensitivity) that is characterized by enhanced activation of endogenous opiates and supraspinal pain modulation systems. To the extent that this hypothesis is true, individual differences in nociceptive responses at rest, during opiate blockade, and during supraspinal activation may be used to predict longitudinal changes in blood pressure. The findings from this project may also help to explain the attenuation of clinical pain (e.g., angina) that can complicate early arid accurate detection of heart disease in individuals with hypertension. Three studies are proposed that will use the nociceptive flexion reflex (NFR), defined as the intensity of sural nerve stimulation required to elicit leg withdrawal, as an objective measure of nociception. Study l will determine NFR thresholds in controls and unmedicated patients with newly-diagnosed hypertension, and will assess endogenous opiates and descending pain modulation as mediators of hypertensive hypoalgesia. Study 2 will determine NFR thresholds in young adults at high and low risk for hypertension (defined by parental history of hypertension and resting blood pressure), and will also assess endogenous opiates and descending pain modulation as mediators of hypoalgesia in those at high risk for hypertension. Study 3 will evaluate NFR thresholds at rest and changes in NFR threshold in response to Supraspinal modulation as predictors of longitudinal changes in blood pressure in young adults at high and low risk for hypertension. The proposed studies are important for several reasons. Studies l and 2 will assess promising mechanisms of hypoalgesia which may lead to important insights concerning the role of endogenous opiates in the pathophysiology of hypertension. Study 3 will evaluate nociceptive responses as a means of identifying those at greatest risk for hypertension among heterogeneous groups of high risk men and women. This information could be used to identify the best candidates for behavioral and other risk reduction efforts.